Genetic polymorphisms of interleukin‐1‐beta in association with sustained response to anti‐viral treatment in chronic hepatitis B in Chinese

• Published in: Alimentary pharmacology & therapeutics Vol. 23; no. 12; pp. 1703 - 1711
• Main Authors: CHAN, H. L.‐Y., TSE, A. M.‐L., ZHANG, M.‐D., WONG, V. W.‐S., CHIM, A. M.‐L., HUI, A. Y., SUNG, J. J.‐Y.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-06-2006; Blackwell
• Subjects: Adult; Antiviral Agents - therapeutic use; Asian Continental Ancestry Group - ethnology; Asian Continental Ancestry Group - genetics; Biological and medical sciences; Digestive system; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis B virus; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - genetics; Human viral diseases; Humans; Infectious diseases; Interferon-alpha - therapeutic use; Interleukin-1 - genetics; Lamivudine - therapeutic use; Male; Medical sciences; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Polymorphism, Genetic - genetics; Recombinant Proteins; Treatment Outcome; Viral diseases; Viral hepatitis; Asia; China; Genetic variability; Cytokine; Hepatic disease; Genotype; Interleukin 1β; Infection; Viral hepatitis B; Virus; Association; Treatment; Viral disease; Digestive diseases; Chinese
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2006.02948.x

Summary
Background
Interleukin‐1β is a pro‐inflammatory cytokine that may influence host defence against viral infection.
Aim
To investigate the impact of interleukin‐1β gene polymorphism on the response to anti‐viral treatment.
Method
Hepatitis B e antigen‐positive chronic hepatitis B patients who have completed a randomized study of peginterferon alpha‐2b and lamivudine combination vs. lamivudine monotherapy were included. Sustained responders were patients who had persistent hepatitis B e antigen loss and less than two occasions with hepatitis B virus DNA >100 000 copies/mL at any time up to week 76 post‐treatment. Polymorphisms at interleukin‐1β‐511, ‐31 and ‐3954 and interleukin‐1 receptor antagonist (RN) were studied.
Results
Eighty‐eight patients were studied and 18 (20%) patients developed sustained response. Near complete linkage disequilibrium was observed between interleukin‐1β‐511 and ‐31 loci. After adjustment for the potential confounding effects of treatment allocation, hepatitis B virus genotype, pre‐treatment alanine aminotransferase and hepatitis B virus DNA levels, genotype C/T at interleukin‐1β‐511 was found to be associated with higher sustained response than genotype C/C (adjusted odds ratio 10.4, 95% CI 1.1, 96.9, P = 0.040). The proportion of sustained responders tend to be higher among patients with allele T at interleukin‐1β‐511 (83%) than those without (70%) (P = 0.058).
Conclusion
High interleukin‐1β production genotype at position ‐511 has a favourable response to anti‐viral treatments.